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Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.
Nrf2 induces interleukin-6 (IL-6) expression via an antioxidant response element within the IL-6 promoter.
J. Biol. Chem. 286, 4493-4499 (2011)
IL-6 gene expression is controlled by a promoter-region containing multiple regulatory elements such as NF-kB, NF-IL6, CRE, GRE and TRE. In this study, we demonstrated that TRE, found within the IL-6 promoter, is embedded in a functional antioxidant response element (ARE) matching an entire ARE consensus sequence. Further, point mutations of the ARE consensus sequence in the IL-6 promoter construct selectively eliminate ARE but not TRE activity. Nrf2 is a redox-sensitive transcription factor which provides cytoprotection against electrophilic and oxidative stress and is the most potent activator of ARE-dependent transcription. Using Nrf2 knockout mice we demonstrate that Nrf2 is a potent activator of IL-6 gene transcription in vivo. Moreover, we show evidence that Nrf2 is the transcription factor that activates IL6 expression in a cholestatic hepatitis mouse model. Our findings suggest a possible role of IL-6 in oxidative stress defence and also give indication about an important function for Nrf2 in the regulation of hematopoietic and inflammatory processes.
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Publication type
Article: Journal article
Document type
Scientific Article
ISSN (print) / ISBN
0021-9258
e-ISSN
1083-351X
Quellenangaben
Volume: 286,
Issue: 6,
Pages: 4493-4499
Publisher
American Society for Biochemistry and Molecular Biology
Reviewing status
Peer reviewed
Institute(s)
Institute of Lung Health and Immunity (LHI)